The role of DNA repair in protecting the cell against mutagens and carcinogens has been suggested by a variety of studies. Most of this work, however, has focused exclusively on the cyclobutane pyrimidine dimer form of damage in ultraviolet (UV) irradiated DNA. The objective of the proposed project is to broaden our knowledge to include nondimer damage in DNA. To this end, a nondimer damage-specific DNA binding protein isolated from human placenta will be employed as a probe for such damage. The protein itself will be examined in terms of its molecular weight, subunit composition, cellular location and binding site amino acid residues. This protein will also be employed in the isolation of nondimer damage from UV-irradiated poly d(A-T) and from UV- and X-irradiated DNA. The sequence/structural specificity of nondimer damage introduction will be examined as will the radiation chemistry of nondimer damage introduction with ionizing radiation. Finally, cell lines from normal individuals as well as those derived from individuals with Fanconi's anemia, xeroderma pigmentosum, ataxia telangiectasia and Bloom's syndrome will be examined both for the presence of binding protein as well as for their ability to remove protein-recognizable sites from their DNA after irradiation.